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K Isobe

Publications and source records attributed to K Isobe.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cyclobilirubin formation by in vitro photoirradiation with neonatal phototherapy light.

BACKGROUND: The main mechanism of phototherapy for neonatal hyperbilirubinemia is the production and excretion of (EZ)- and (EE)-cyclobilirubin (4E,15Z- and 4E,15E-cyclobilirubin). Thus, the clinical efficacy of the light source for phototherapy must be evaluated by cyclobilirubin formation from (ZZ)-bilirubin in in vitro photoirradiation. METHODS: In the present study, we investigated the in vitro production pattern of bilirubin photoisomers by phototherapy light from the bilirubin-human serum albumin complex. RESULTS: No clear difference was found in the curves relative to (ZZ)-bilirubin and its photoisomers under aerobic and anaerobic conditions. The ratio of (EZ)-cyclobilirubin to (ZZ)-bilirubin increased proportionately to the dose of irradiating light and no photoequilibrium state was observed analogous to that found in configurational photoisomerization. The concentration of (EZ)- and (EE)-cyclobilirubin increased proportionately with the grade of the percentage decrease in A(460 nm) from 0 to 23%. With a percentage decrease in A(460 nm) of 23% or more, the cyclobilirubin concentrations reached a steady state. The reason for this appears to be that the concentration of (ZZ)-bilirubin, a substrate for photoisomers, dropped below 1 mg/100 mL. Biliverdin was produced only in trace amounts. However, the absorption at 520--700 nm increased after a percentage decrease in A(460 nm) of more than 23%. CONCLUSIONS: The results of the present study show that little bilirubin photooxidation occurred with in vitro aerobic photoirradiation. Before the concentration of cyclobilirubin reaches a steady state, it is theoretically valid to use the percentage decrease in A(460 nm) for the evaluation of the clinical efficacy of the light source.

Bilirubin↗
PubMed2001

Cerebral metabolism and regional cerebral blood flow during moderate systemic cooling in newborn piglets.

BACKGROUND: Clinical trials of hypothermic therapy in asphyxiated infants have started recently. However, clinical studies have been delayed by the difficulty in selecting infants with a bad neurological prognosis and by the concern regarding adverse effects of hypothermia. The purpose of this study is to examine the effects of systemic cooling on cerebral metabolism (CMR) and the regional cerebral blood flow (rCBF) in newborn piglets. METHODS: The rCBF in the seven parts of the brain were measured with colored microspheres. The blood samples for the measurement of cerebral oxygen consumption (CMRO2) and cerebral glucose consumption (CMRglc) was collected from the umbilical artery and the superior sagittal sinus. RESULTS: Reductions of cerebral cortex temperature to 32 degrees C decreased blood flow in all brain regions. In particular, blood flow in the brainstem decreased more significantly than in any other region. The total cerebral blood flow (CBF), CMRO2 and CMRglc, respectively, decreased to 32.3+/-3.9 mL/100 g per min, 2.8+/-1.0 mLO2/100 g per min and 22+/-12 mmol/100 g per min at 32 degrees C (41, 53 and 46% of the initial value). The CBF decreased in parallel with CMRO2 and CMRglc down to 35 degrees C, but CBF decreased to a greater extent than CMRO2 and CMRglc at below 35 degrees C. CONCLUSIONS: The indication of hypothermic therapy and the degree of cooling have to be performed very carefully. Systemic cooling is especially dangerous for the total asphyxiated infants who might have damage to the brainstem because the blood flow in the brainstem has significantly decreased during hypothermia.

Animals↗
PubMed2001

Outcome prediction in severe head injury: analyses of clinical prognostic factors.

Retrospective analysis of 272 patients with severe head injury was performed. Patient age, Glasgow Coma Scale (GCS) score, pupillary abnormalities, impaired oculocephalic response, presence of subarachnoid haemorrhage, and multiplicity of parenchymal lesions on computerised tomography (CT) were examined. The CT findings were divided into 2 groups, diffuse brain injury (DBI) and mass lesion, according to the classification of the Traumatic Coma Data Bank. The DBI, basically, has no high or mixed density lesion more than 25 ml on CT, and was classified into 4 subgroups: DBI I includes injuries where there is no visible pathology; DBI II includes all injuries in which the cisterns are present with a midline shift of less than 5 mm; DBI III includes injuries with swelling where the cisterns are compressed or absent and the midline shift is less than 5 mm; DBI IV includes injuries with a midline shift of more than 5 mm. The mass lesions were categorised into 3 subgroups: epidural haematoma; acute subdural haematoma; and intracerebral haematoma. Outcomes were determined at 6 months following trauma using the Glasgow Outcome Scale. All DBI I patients recovered well. In the DBI II group, age, GCS score and detection of multiple parenchymal lesions on CT were significantly correlated with outcome. For the DBI III and IV groups, the only significant prognostic factor was the GCS score. In patients with a mass lesion, the GCS score was the only significant prognostic factor in the epidural haematoma group, but the GCS score and the presence of subarachnoid haemorrhage were predictive factors in the acute subdural haematoma group. Outcomes were unfavourable in the majority of patients with intracerebral haematoma. GCS score could predict outcome in all groups. The confidence of the outcome prediction ranged from 75.8 to 92.1%, depending on logistic regression analysis.

Adolescent↗
PubMed2001

Angiotensin subtype-2 receptor (AT2 ) negatively regulates subtype-1 receptor (AT1 ) in signal transduction pathways in cultured porcine adrenal medullary chromaffin cells.

BACKGROUND: Two distinct types of angiotensin II (AngII) receptors, AT1 and AT2, have been cloned. We have shown previously that stimulation of AT2 reduces intracellular cyclic guanosine monophosphate (cGMP) levels in cultured porcine chromaffin cells in which AT2 is the predominantly expressed receptor. However, it has not been determined whether AT1 or AT2 affects signal transduction pathways involving mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STATs) in chromaffin cells. Also, it is unclear whether cGMP/protein kinase G (PKG) is involved in the regulation of MAPKs and STATs in these cells. DESIGN: Chromaffin cells were derived from porcine adrenal medulla. The effects of AngII alone (representing physiological conditions), AngII plus CV-11974 (an AT1 antagonist, which simulates specific AT2 stimulation), AngII plus PD 123319 (an AT2 antagonist, which simulates specific AT1 stimulation), and 8-Br-cGMP (a membrane-permeable cGMP analogue) alone on MAPKs (ERKs, JNK, p-38 MAPK) and STATs (STATs 1, 3 and 5) activity were measured. METHODS: Phosphorylated MAPKs (extracellular signal-related kinases (ERKs), c-jun N-terminal kinase (JNK) and p38 MAPK) and STATs (STATs 1, 3 and 5) were measured by immunoprecipitation-Western blot analysis (IP-Western blot). RESULTS: AT1 stimulation markedly increased expression of ERKs, JNK, p38 MAPK via Ca2+-dependent protein kinase C (PKC) isoforms (cPKC), as well as STATs 1, 3 and 5 in cultured porcine chromaffin cells. In contrast, AT2 stimulation markedly decreased the expression of these signaling molecules. Also, 8-Br-cGMP alone induced increases in ERKs, JNK, p38 MAPK, and STATs 1, 3 and 5. Because AT2 inhibits cGMP production, we speculate that AT2 may act to suppress cGMP production, which in turn reduces the activity of both MAPKs and STATs in chromaffin cells. CONCLUSION: AT2 negatively regulates AT1 in signal transduction pathways in chromaffin cells.

Angiotensin II↗
PubMed2001

Time of closure of ductus venosus in term and preterm neonates.

AIM: To investigate the relation between gestational age, birth weight, and antenatal corticosteroid administration and the time of ductus venosus closure. METHODS: Ninety eight neonates of 30-41 weeks gestational age were studied by daily ultrasonography until ductus venosus closure. RESULTS: In neonates of 30-33 weeks gestational age, the ductus venosus closed at 6.0 (2.4)days (mean (SD)); in those of 34-36 weeks gestational age, it closed at 6.1 (2.8) days; and in those of 37-41 weeks gestational age, it closed at 4.2 (2.1) days. The effect of antenatal administration of corticosteroids on the time of closure was also investigated in neonates of 30-34 weeks gestational age. Closure occurred by 5.5 (2.4) days in the group given corticosteroids compared with 7.5 (2.1) days in the remainder. CONCLUSIONS: The ductus venosus closed sooner after birth in neonates of greater gestational age or higher birth weight. Antenatal corticosteroid administration had a significant effect in promoting closure.

Birth Weight↗
PubMed2001

Ca(2+) mobilization, tyrosine hydroxylase activity, and signaling mechanisms in cultured porcine adrenal medullary chromaffin cells: effects of leptin.

Leptin acts as a satiety factor, but there is also evidence that it affects energy expenditure. Leptin's effects are mediated by its receptors, which function as activators of a Janus family of tyrosine kinases-signal transducer and activator of transcription (JAK-STAT) pathway. We have previously shown that murine recombinant leptin markedly induces both the release of catecholamine and tyrosine hydroxylase (TH) (rate-limiting enzyme in the biosynthesis of catecholamine)-messenger RNA (mRNA) levels, probably through Ob-Rb expressed in cultured porcine chromaffin cells. In the present study, we examined the effect of leptin on Ca(2+) mobilization, TH enzyme activity, and signaling. Ca(2+) channel blockers, nicardipine and omega-Conotoxin GVIA, each at 1 microM, were effective in inhibiting leptin-induced catecholamine secretion. When intracellular Ca(2+) ([Ca(2+)](i)) was measured in fura 2-loaded chromaffin cells, leptin was found to cause a sustained increase of Ca(2+) by mobilizing Ca(2+) from both extra- and intracellular pools. Additionally, leptin significantly stimulated inositol 1.4.5-triphosphate IP(3) production in a dose-dependent manner. TH-activity is regulated by both TH enzyme activity and increased TH-mRNA levels accompanied by increased TH protein synthesis. Leptin (>/=1 nM) significantly stimulated TH enzyme activity and increased the TH protein level, indicating that it stimulates catecholamine biosynthesis. In addition, removal of external Ca(2+) completely inhibited leptin (100 nM)-induced TH enzyme activity. Leptin (>/=1 nM) caused an increase in the activity of mitogen-activated protein kinases (MAPKs) that was accompanied by increased phosphorylation of STAT-3 and -5, but not STAT-1. Moreover, MAPK activity evoked by leptin(100 nM) and TH-mRNA caused by leptin (10 nM) were inhibited by 50 and 30 microM of PD-98059 (the MAP kinase kinase-1 inhibitor), respectively. These findings indicate that leptin activates voltage-dependent Ca(2+) channels (VDCC), presumably L-type and N-type Ca(2+) channels, as well as phospholipase C, and suggest that leptin-induced catecholamine secretion is mainly mediated by activation of VDCC. In addition, leptin stimulates the JAK-STAT pathway as well as increasing the levels of TH-mRNA levels through the MAPK pathway in porcine chromaffin cells.

Adrenal Medulla↗
PubMed2001

Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells.

We have previously shown that murine recombinant leptin directly stimulates catecholamine synthesis through the long form of the leptin receptor (Ob-Rb) expressed in cultured porcine chromaffin cells. Additionally, we found that leptin activates IP3 production after PLC activation. It is well established that activation of PLC elicits IP3 production as well as an increase in diacylglycerol, a compound that stimulates PKC. Therefore, we investigated the involvement of PKC in leptin-induced catecholamine synthesis. Leptin was found to induce significant increases in PKC activity in a dose-dependent manner (1, 10, and 100 nM); chelation of extracellular Ca(2+) by EDTA abolished this PKC stimulatory activity. We also confirmed by Western blot analysis that leptin (at 100 nM) induced significant increases in Ca(2+)-dependent PKC alpha, -beta(I), and -gamma expression. The activity of the rate-limiting enzyme tyrosine hydroxylase (TH) in the biosynthesis of catecholamine is regulated at the transcriptional and posttranscriptional levels. TH enzyme activity and TH mRNA levels induced by 100 nM leptin were significantly inhibited by the PKC inhibitor Ro 32-0432 as well as by EDTA. In addition, increases in TH protein and intracellular catecholamine content stimulated by leptin were completely inhibited by Ro 32-0432. Leptin markedly activated ERKs and, to a lesser extent, JNK; these stimulatory effects on ERKs and JNK were completely inhibited by Ro 32-0432 as well as EDTA. In contrast, leptin did not activate P38 MAPK. Similar to leptin, PMA activated ERK and JNK. Nicardipine and omega-conotoxin GVIA, each at 1 microM, were effective at inhibiting leptin-induced TH enzyme activity, TH mRNA accumulation, PKC activity, and ERK activity. Leptin increased activating protein-1 DNA-binding activity, and this was diminished by Ro 32-0432 as well as EDTA, similar to the reduction of TH mRNA levels. In addition, using supershift analysis, we documented the involvement of c-Fos and, to a lesser extent, c-Jun in leptin-induced activating protein-1 activity. These results indicate that leptin stimulates Ca(2+)-dependent PKC isoform-dependent catecholamine synthesis in porcine chromaffin cells. Previously, we had shown that leptin stimulated cAMP. The present study also showed that H89 (a PKA inhibitor) moderately, but significantly, inhibited leptin-induced ERK and TH mRNA. Consistent with this finding, leptin is shown here to activate novel PKC epsilon, which is assumed to stimulate Raf, upstream of ERKs, via cAMP, supporting the suggestion that Ca(2+)-independent novel PKC may also play some physiological role in regulating catecholamine synthesis.

Adrenal Medulla↗
PubMed2001

Activation of angiotensin II subtype 2 receptor induces catecholamine release in an extracellular Ca(2+)-dependent manner through a decrease of cyclic guanosine 3',5'-monophosphate production in cultured porcine adrenal medullary chromaffin Cells.

We have previously demonstrated that CGP 42112 (AT(2) agonist > or =1 nM) markedly reduces catecholamine biosynthesis through AT(2), which is the major angiotensin II (AngII) receptor subtype in cultured porcine chromaffin cells. Also, we have shown that CGP 42112 (> or =1 nM) induces a reduction in cGMP production in these cells. The present study showed that AngII reduced cGMP production via AT(2) in a manner similar to that found with CGP 42112. AngII (1 nM) significantly increased catecholamine secretion from cultured porcine adrenal medullary chromaffin cells. The stimulation was significantly inhibited by PD 123319 (AT(2) antagonist). The stimulation was moderately, but significantly, attenuated by CV-11974 (AT(1) antagonist, > or =10 nM), suggesting an involvement of AT(1). Moreover, CGP 42112 (> or =10 nM) markedly increased catecholamine release from these cells. The stimulation by CGP 42112 was abolished by PD 123319, whereas CV-11974 had no effect, indicating that this response is also mediated by AT(2). We further examined whether extracellular Ca(2+) is involved in the stimulatory effect of AT(2) on catecholamine secretion. Removal of external Ca(2+) significantly suppressed either AngII plus CV-11974 (100 nM; which simulates specific AT(2) stimulation) or CGP 42112- induced catecholamine secretion. AngII plus CV-11974 or CGP 42112 caused a sustained increase in intracellular Ca(2+) ([Ca(2+)](i)), as determined in fura-2-loaded chromaffin cells in an extracellular Ca(2+)-dependent manner. In the presence of EGTA, the subsequent addition of AngII with CV-11974 and CGP 42112 did not cause any increase in [Ca(2+)](i) levels. Consistent with this finding, CGP 42112 (10 nM to 1 microM) did not alter inositol triphosphate (IP(3)) production, a messenger for mobilization of Ca(2+) from intracellular storage sites. In addition, the intracellular Ca(2+) chelator 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'- tetraacetic acid acetoxymethylester (BAPTA) did not affect CGP 42112-induced catecholamine release. We tested whether a decrease in cGMP was the cause of the stimulatory effect of AT(2) on catecholamine secretion. Pretreatment with 8-bromo-cGMP (1 mM) prevented the stimulatory effect of AngII plus CV-11974 and CGP 42112 on both catecholamine secretion and [Ca(2+)](i). When 8-bromo-cGMP was added after application of AngII plus CV-11974 or CGP 42112, [Ca(2+)](i) induced by these agents was gradually reduced toward the baseline values. Similarly, guanylin completely abolished the AngII- plus CV-11974-induced increase in both NE secretion and [Ca(2+)](i). The Ca(2+) channel blockers, nicardipine and omega-conotoxin G VIA, at 1 microM in both cases, were also effective in inhibiting AT(2) stimulation-induced secretion. On the other hand, neither T-type voltage-dependent Ca(2+) channel blockers, flunarizine, nor Ni(2+) affected catecholamine release caused by AT(2) stimulation. These findings demonstrate that AT(2) stimulation induces catecholamine secretion by mobilizing Ca(2+) through voltage-dependent Ca(2+) channels without affecting intracellular pools and that these effects could be mediated by a decrease in cGMP production.

Adrenal Medulla↗
PubMed2001

Relationships between serum (ZZ)-bilirubin, its subfractions and biliverdin concentrations in infants at 1-month check-ups.

In 150 infants, including those with breast milk jaundice, who were brought to our hospital for their 1-month check-ups, the serum concentrations of (ZZ)-bilirubin, its subfractions and biliverdin were measured by high-performance liquid chromatography and the relationships among them investigated. (ZZ)-Bilirubin was found to have the highest serum concentration, followed by (ZE)-bilirubin, accounting for 14.0 (geometric mean) % of (ZZ)-bilirubin. Biliverdin had a serum concentration of 0.95% of (ZZ)-bilirubin. There was only a small amount of total (di- and mono-) glucuronosyl bilirubin, 0.42% of (ZZ)-bilirubin. (ZE)-Bilirubin, (EZ)-bilirubin, (EZ)-cyclobilirubin. biliverdin, diglucuronosyl bilirubin and monoglucuronosyl bilirubin (C-8 and C-12) showed positive logarithmic correlations with (ZZ)-bilirubin (R2=0.16 or above, P<0.05). (ZE)-Bilirubin showed a significant positive logarithmic correlation with (ZZ)-bilirubin (R2=0.863, P<0.0001). Furthermore, (EZ)-cyclobilirubin, the most important photoisomer in phototherapy for neonatal hyperbilirubinaemia, was detected in very small amounts in approximately half of the neonates (84 of 150) when they were in conditions of only weak ambient light. The relationship between total glucuronosyl bilirubin and (ZZ)-bilirubin concentrations fitted a model of saturation kinetics of bilirubin UDP-glucuronosyltransferase.

Bilirubin↗
PubMed2001

Detection of nasopharyngeal carcinoma: fast short time inversion recovery images compared with fat suppression, contrast enhanced T(1) weighted spin echo images.

The aim was to compare fast short time inversion recovery (FSTIR) images and fat suppression, contrast enhanced T(1) weighted (FSCE T1W) spin echo images in the diagnosis of nasopharyngeal carcinoma (NPC). 102 MR studies were obtained with a 1.0 T or a 1.5 T system in 28 patients with NPC. The MR studies comprised both FSTIR and FSCE T1W images. FSTIR and FSCE T1W images were compared for detection of NPC by means of a receiver operating characteristic (ROC) analysis. The areas under the ROC curves of FSTIR and FSCE T1W images showed no statistical difference (0.87 vs 0.87). There was also no statistical difference in the sensitivity, specificity and accuracy of each sequence (0.74 vs 0.77, 0.81 vs 0.77 and 0.79 vs 0.77, respectively). Both sequences had the same performance for detection of NPC. FSTIR is as useful as FSCE T1W images, especially in the detection of recurrent tumours, but without the cost of contrast medium.

Adult↗
PubMed2001

Natural history of scoliosis in children with syringomyelia.

We performed a retrospective review of 27 scoliotic patients with syringomyelia using MRI. Their mean age at the first MRI examination was 10.9 years, and at the final review 15.8 years. The mean ratio of the diameter of the syrinx to the cord on the midsagittal MRI (S/C ratio) decreased from 0.49 to 0.24; 14 patients showed a decrease of 50% or more (reduction group). In this reduction group, the cerebellar tonsillar herniation decreased from a mean of 11.3 mm to 6.0 mm, and some improvement in dissociated sensory disturbance was seen in nine of 13 patients. The scoliosis improved by 5 degrees or more in six patients in the reduction group. Our results indicate that spontaneous shrinkage of syringomyelia in children is not unusual and is associated with improvement in the tonsillar herniation, the scoliosis and the neurological deficit.

Adolescent↗
PubMed2001

Immunoglobulin heavy chain variable region (VH) genes of B cell chronic lymphocytic leukemia cells from lymph nodes show somatic mutations and intraclonal diversity irrespective of follicular dendritic cell network.

We analyzed the immunoglobulin heavy chain variable region (VH) gene in 4 Japanese cases of B cell chronic lymphocytic leukemia (B-CLL) with enlarged lymph nodes to clarify the presence of somatic mutations and intraclonal diversity. We also attempted to determine the role of the follicular dendritic cell (FDC) network in some proliferation centers, where tumor cells are mitotically active. Immunohistochemical studies revealed that all 4 cases showed the typical immunophenotype: CD5+, CD23+, IgM+ and IgD+. DNA was extracted from paraffin sections (lymph node) and rearranged VH gene was amplified by PCR. All but one exhibited a moderate number of somatic mutations, with percentages ranging from 4.1 to 9.5, and one of which indicated the effect of antigen selection on its VH gene. Multiple clone analysis of whole tissues showed intraclonal diversity in one case, whose VH gene carried a somatic mutation but the effect of antigen selection was not apparent. We further examined microdissected tissues to elucidate the relationship between FDC network and VH gene status in 2 cases. In one case, intraclonal diversity was not apparent irrespective of FDC network, however, both tumor cells around the FDC network and those apart from the FDC showed signs of intraclonal diversity in another case, suggesting that intraclonal diversity was not related to the FDC network in B-CLL. Here we demonstrate that some cases of B-CLL involved in lymph node carried mutated VH genes and showed intraclonal diversity like the tumor cells in the peripheral blood. However, the significance of the FDC network in the proliferation center still remains to be resolved.

Amino Acid Sequence↗
PubMed2001

Cell killing and mutation induction by heavy ion beams.

Carbon beam radiotherapy for cancer patients was initiated in Japan in June 1994. This study attempts to clarify the radiobiological effects of heavy ion beams. In this study, human cancer cell lines (RMG-1, MDA-MB231) and V79 cells were used. The cell killing was determined by colony forming assay, and mutation induction was determined by counting the number of 6-thioguanine resistant colonies (hprt locus mutation assay). The cell lines were irradiated with carbon (20 or 80 keV/microm) or neon beams (80 keV/microm). Carbon ions with a higher LET value (80 keV/microm) had an enhanced cytotoxic effect compared to those with a lower LET value (20 keV/microm). Carbon beams produced a slightly stronger cytotoxic effect than neon beams when irradiated at the same LET level (80 keV/microm), but the difference was not remarkable. The mutant fraction was significantly higher in all cell lines when they were irradiated with heavy ion beams, compared to the results for X-ray irradiation. The mutant fraction increased when the LET of the carbon beams increased. At equivalent LET values, the mutant fraction was lower for neon beams than for carbon beams. Fractionation of carbon beam irradiation had no effect on survival, but reduced the mutant fraction. Neon beams might be more appropriate for heavy ion therapy, especially when higher doses are being used. In addition, the fractionation of heavy ion beam administration might be appropriate for reducing the mutant fraction.

Animals↗
PubMed2000

Interaction between DNA-damage protein GADD34 and a new member of the Hsp40 family of heat shock proteins that is induced by a DNA-damaging reagent.

GADD34 is one of a subset of proteins induced after DNA damage or cell growth arrest. To examine the function of GADD34, we used the yeast two-hybrid system to clone the protein that interacts with murine GADD34. As bait we used the product of the partial GADD34 cDNA, including the regions rich in proline, glutamic acid, serine and threonine (PEST) and gamma(1)34.5 regions. A cDNA clone, named GAHSP40, which is a mouse DnaJ family protein with a high similarity to human HLJ1 was cloned. The interaction between GADD34 and GAHSP40 in cultured cells was confirmed by a co-immunoprecipitation experiment and in NIH 3T3 cells by two-hybrid analysis in vivo. For binding of the two proteins, the gamma(1)34.5-similar region of GADD34 was necessary; however, the PEST region was also involved and the C-terminus of GAHSP40, but not the J-domain, was important. GAHSP40 was detected in all mouse tissues examined, but a different transcript was found in the testis. Both GADD34 mRNA and GAHSP40 mRNA were significantly elevated by treatment with methyl methanesulphonate, although the time courses were different. In addition, both GAHSP40 and GADD34 mRNA were induced by heat shock.

3T3 Cells↗
PubMed2000

A patient with type 2 diabetes mellitus associated with mutations in calcium sensing receptor gene and mitochondrial DNA.

A 44-year-old female with familial hypocalciuric hypercalcemia (FHH) due to a homozygous missense mutation (Pro40Ala) in calcium sensing receptor (CaSR) gene has type 2 diabetes mellitus. The identical heterozygous mutation of CaSR gene was observed in consanguineous parents and all other family members examined except her two sisters. Many subjects with abnormal glucose tolerance were observed in this family, which is compatible with maternal inheritance. Mitochondrial function of complex I (NADH-coenzyme Q reductase) activity in cybrid cells between mitochondrial DNA (mtDNA)-deleted (rho(0)) HeLa cells and mtDNA from the proband was decreased by 35%. The proband has eight substitutions and among these 4833 A/G is a missense substitution in NADH dehydrogenase 2 gene and may probably be a major pathogenic mutation of impaired complex I activity. These results suggest that coexistence of nuclear gene and mtDNA mutations may have caused or modified the development of abnormal glucose tolerance in this family.

Adult↗
PubMed2000

The diagnostic significance of left auricular thrombus in F344/N rats.

In the process of assessing the main cause of death in F344/N rats from the aging farm of our institute, we have often found left auricular thrombus in autopsy cases of moribund animals. In 319 autopsy cases, 45 were of left auricular thrombus and 44 were accompanied by hematopoietic neoplasms, including overt leukemia and a pre-leukemic condition of leukemia. In cases without splenomegaly, this lesion was found in 13 of 21 animals (61.9%) whereas, in cases with splenomegaly, 31 of 239 were positive for this lesion (13.0%). Thus, left auricular thrombus may be an important macroscopic diagnostic criteria of hematopoietic neoplasms, especially when splenomegaly is absent. Furthermore, this lesion tended to arise in aged animals despite the presence of splenomegaly. These results would therefore greatly contribute to aging science by confirming the health condition of experimental rats and the accuracy of subsequent results.

Journal Article↗
PubMed2000

Target volume definition for upper abdominal irradiation using CT scans obtained during inhale and exhale phases.

PURPOSE: To evaluate the clinical utility of a treatment-planning technique involving the use of CT images obtained during both the static exhalation phase and static inhalation phase (two-phase planning). METHODS AND MATERIALS: Ten patients with pancreatic or liver tumors underwent CT scanning under static exhale and inhale conditions, after a period of mild ventilation. By setting image positions differently, we were able to treat the two-phase images as one dataset. Each gross tumor volume (GTV) was contoured separately and the mixed GTV was used for the two-phase treatment planning. Treatment plans were constructed to compare the two-phase plans with the plans constructed using static exhalation images. The shift of the center of the GTV and kidneys and the minimum dose of GTV were then calculated. RESULTS: The shift of the GTV ranged from 2.6 to 27. 3 mm and that of the kidneys from 2.2 to 24 mm. In some patients whose treatment was planned using exhalation planning, the minimum dose of GTV at inhalation was less than 90% of the isocenter dose. CONCLUSION: Two-phase planning is a simple technique that can visualize tumor and organ movement simultaneously using CT. It further defines adequate field margins around the tumor and prevents unexpected radiation exposure to critical organs. Routine use of this technique for upper abdominal irradiation is recommended.

Abdominal Neoplasms↗